Diuretic Effect Research Articles

PENGARUH SUHU PENYEDUHAN TERHADAP EFEK DIURETIK TEH HIJAU PADA MENCIT JANTAN GALUR SWISS

Tea (Camelia sinensis L.) is a beverage that is familiar to the community and is drunk by brewing it. Green tea contains chemicals such as polyphenols, tannins, steroids and flavonoids. This study aimed to determine the effect of temperature brewing of green tea in the diuretic effect of male swiss strain mice. This research is an experimental study with 25 mice which were divided into five groups, group I (CMC Na 1%), Group II (Furosemide dose 5.2 mg/KgBB), Group III,IV and V (green tea brewed at 50oC,70oC dan 90oC ) with a brewing time of 5- 15 minutes. Urine measurements were performed every 1 hour for 6 hours. Data analysis was carried out using the One-Way ANOVA test followed by the LSD test with a 95% confidence level. The results showed that the diuretic effect at a brewing temperature of 50oC was not significantly different (p> 0.05) with the diuretic effect at 70oC but the average volume of urine at 50oC was greater than 70oC. Diuretic effect at temperature 90oC was significantly different (p<0.05) compared to 50oC and 70oC. The diuretic effect of green tea can be optimal, if the brewed at a temperature of 50oC and 70oC for 5-15 minutes

UJI INVIVO AKTIVITAS DIURETIKA EKSTRAK ETANOL 70% DAUN UNGU (Graptophyllum pictum (L) Griff) PADA MENCIT PUTIH JANTAN GALUR WISTAR

Traditionally, daun ungu plant (Graptophyllum pictum (L) Griff) has been known to have pharmacological effects that can help with a variety of health issues. This plant’s flavonoid compounds content is thought to have diuretic activity in this plant is believed to have activity. The purpose of this study is to determine the diuretic activity and optimal dose of etanol extract of 70% daun ungu administered orally to male white mice. This is an experimental study with a completely randomized design (CRD) that includes 1 negative control group (Na.CMC 0.5%), 1 positive control group (furosemide 40 mg) and 3 test groups of 70% daun ungu ethanol extract doses of 10 mg/kg BW, 25 mg/kg BW and 40 mg/kg BW with urine volume test parameters. One-way ANOVA and Kruskal-Wallis statistical test were used to analyze the data. The results showed that one-way ANOVA revealed a P < 0.05 (0.012), and P ≤ 0.05 (0.051) for the Kruskal-Wallis test. It can be concluded that 70% daun ungu etahanol exctract has effective diuretics, with an optimal dose of 40mg/Kg BW providing an effect twice as large as the positive control (furosemide 40 mg).

Advanced heart failure: parenteral diuretics for breathlessness and peripheral oedema – systematic review

BackgroundAdvanced heart failure patients suffer with breathlessness and peripheral oedema, which are frequently treated with parenteral diuretics despite limited evidence.AimTo analyse the effectiveness of parenteral diuretics on breathlessness and peripheral...

Sodium Glucose Co-Transporter-2 (SGLT 2) Inhibitor as A Therapy For Heart Failure With Low Ejection Fraction (HFrEF)

Heart failure is a major cause of cardiovascular morbidity and mortality worldwide despite advances in prevention and management. Recent clinical trial findings have shown that sodium-glucose co-transporter 2 inhibitor (SGLT2i) produces effects other than lowering blood glucose levels, i.e., exhibits beneficial cardiovascular effects. The purpose of this paper is to determine the role of SGLT2i in heart failure patients with low ejection fraction (HFrEF) so that it can be used as a guide for future management. This study is a narrative review by searching on Google Scholar through several keywords. The period including articles obtained is articles from 2014 to 2022. The diuretic effect of SGLT2i can cause an increase in cardiac preload. The reduction in cardiac afterload likely occurs through a decrease in blood pressure and arterial stiffness resulting in increased endocardial blood flow. SGLT2i has a beneficial effect on the heart remodeling process. SGLT2i can prevent heart failure by increasing the production of ATP from the oxidation of ketone bodiesSGLT2i in heart failure patients can reduce blood pressure, maintain a decrease in eGFR and reduce the risk of acute kidney injury (AKI) in patients. SGLT2i is very effective in the treatment of HFrEF patients. Because of these advantages, further research is needed in Indonesia in order to determine the effectiveness and impact of giving SGLT2i to HFrEF patients in Indonesia.

Design and search for prospective diuretics (CA II Inhibitors) among aroylhydrazones of esters quinone oxime using in silico and in vivo methodology

The design and search for new selective inhibitors of CA II with a better pharmacological profile, which would cause minimal electrolyte disturbances in the body, remains an urgent problem of medical chemistry and pharmacology today. It is important that the discovered new classes of inhibitors do not always contain the main “pharmacophoric” function (sulfamide), which is characteristic of “classic” drugs (Acetazolamide, Methazolamide, Ethoxzolamide, Dorzolamide and others), but are derivatives of phenols, polyamines, coumarins/thiocoumarins, ureas, thioureas, hydroxamates, etc. These molecules also bind in the active site of the enzyme, but do not interact directly with the catalytic zinc ion or interact through zinc-coordinated water molecules/hydroxide ion. However, this leads to an increase in their selectivity and, as a result, pharmacological action. Continuing the search for compounds that affect urination, we were interested in aroylhydrazones of esters of quinone oxime. Firstly, they are characterized by certain structural features (dynamic and geometric isomerism); secondly, they exhibit redox properties; thirdly, the presence of aromatic fragments makes it possible to create a voluminous combinatorial library for analysis. These compounds are ligands in complexation reactions, and an additional increase in the number of hydrogen acceptors in the molecule due to structural modification will improve ligand-enzymatic interactions with carbonic anhydrase (CAII) and, as a result, reveal new promising diuretics. The aim – design and search for potential diuretics (CA II inhibitors) among aroylhydrazones of esters of quinone oxime using in silico, traditional synthesis and in vivo methodologies. Methods of organic synthesis, physico-chemical methods of analysis of organic compounds (NMR 1H-spectroscopy, elemental analysis). Prediction of affinity to the biological target, prediction of toxicity and lipophilicity of the combinatorial library of benzohydrazides O-aroyl esters of quinone oxime using computer services. The study of compounds affecting the excretory function of rat kidneys was carried out according to the generally accepted method of E.B.Berkhin with water load. The investigation of the probable mechanism was carried out using flexible molecular docking, as an approach to search for molecules that have affinity for human carbonic anhydrase type II (CA II). Macromolecular data of the crystal structure of CA II (PDB ID – 3HS4) were downloaded from the Protein Data Bank (PDB). The design was developed and the search for diuretic agents among benzohydrazides of O-aroyl esters of quinone oximes was developed using in silico methods (prediction of affinity, lipophilicity, toxicity and enzyme-ligand interactions), traditional organic synthesis, and in vivo methods (effect on excretory function of rat kidneys). The synthesis of benzohydrazides of O-aroyl esters of quinone oxime was carried out by the interaction of aroylhydrazines with 4-[(aroylimino)]cyclohexa-2,5-dien-1-ones. The structure of the synthesized compounds was confirmed by elemental analysis and 1H NMR spectra. Studies of the effect of synthesized compounds on the excretory function of rat kidneys allowed us to identify a number of promising compounds among aroylhydrazones of quinonexime esters, which increase daily diuresis by 54.2-352.8% compared to the control group. At the same time, it was established that the most active was N'-(4-[(2-chlorobenzoyloxy)imino]cyclohexa-2,5-dien-1-ylidene)-3-nitrobenzohydrazide, which increased daily diuresis by 352.8% in comparison with the control group, while exceeding the effect of “Hydrochlorothiazide” (170.8%). The developed and implemented strategy for the search for diuretics among benzohydrazides of O-aroylesters of quinone oxime allowed the identification of an effective compound, which in terms of diuretic effect exceeds the comparison drug “Hydrochlorothiazide”. Visualization of the molecular docking of the active compounds showed that their geometry makes it difficult to place them in the pocket of the active site of CA II, but the pronounced diuretic effect can also be associated with their ability to form coordination bonds with the zinc cation. The obtained results justify the further targeted search for potential diuretics among this class of compounds for a more detailed understanding and study of the mechanism of action.

Loss of Slc12a2 specifically in pancreatic β-cells drives metabolic syndrome in mice.

The risk of type-2 diabetes and cardiovascular disease is higher in subjects with metabolic syndrome, a cluster of clinical conditions characterized by obesity, impaired glucose metabolism, hyperinsulinemia, hyperlipidemia and hypertension. Diuretics are frequently used to treat hypertension in these patients, however, their use has long been associated with poor metabolic outcomes which cannot be fully explained by their diuretic effects. Here, we show that mice lacking the diuretic-sensitive Na+K+2Cl-cotransporter-1 Nkcc1 (Slc12a2) in insulin-secreting β-cells of the pancreatic islet (Nkcc1βKO) have reduced in vitro insulin responses to glucose. This is associated with islet hypoplasia at the expense of fewer and smaller β-cells. Remarkably, Nkcc1βKO mice excessively gain weight and progressive metabolic syndrome when fed a standard chow diet ad libitum. This is characterized by impaired hepatic insulin receptor activation and altered lipid metabolism. Indeed, overweight Nkcc1βKO but not lean mice had fasting and fed hyperglycemia, hypertriglyceridemia and non-alcoholic steatohepatitis. Notably, fasting hyperinsulinemia was detected earlier than hyperglycemia, insulin resistance, glucose intolerance and increased hepatic de novo gluconeogenesis. Therefore, our data provide evidence supporting the novel hypothesis that primary β-cell defects related to Nkcc1-regulated intracellular Cl-homeostasis and β-cell growth can result in the development of metabolic syndrome shedding light into additional potential mechanisms whereby chronic diuretic use may have adverse effects on metabolic homeostasis in susceptible individuals.

The loop diuretic torasemide but not azosemide potentiates the anti-seizure and disease-modifying effects of midazolam in a rat model of birth asphyxia

Loop diuretics such as furosemide and bumetanide, which act by inhibiting the Na-K-2Cl cotransporter NKCC2 at the thick ascending limb of the loop of Henle, have been shown to exert anti-seizure effects. However, the exact mechanism of this effect is not known. For bumetanide, it has been suggested that inhibition of the NKCC isoform NKCC1 in the membrane of brain neurons may be involved; however, NKCC1 is expressed by virtually all cell types in the brain, which makes any specific targeting of neuronal NKCC1 by bumetanide impossible. In addition, bumetanide only poorly penetrates the brain. We have previously shown that loop diuretics azosemide and torasemide also potently inhibit NKCC1. In contrast to bumetanide and furosemide, azosemide and torasemide lack a carboxylic group, which should allow them to better penetrate through biomembranes by passive diffusion. Because of the urgent medical need to develop new treatments for neonatal seizures and their adverse outcome, we evaluated the effects of azosemide and torasemide, administered alone or in combination with phenobarbital or midazolam, in a rat model of birth asphyxia and neonatal seizures. Neither diuretic suppressed the seizures when administered alone but torasemide potentiated the anti-seizure effect of midazolam. Brain levels of torasemide were below those needed to inhibit NKCC1. In addition to suppressing seizures, the combination of torasemide and midazolam, but not midazolam alone, prevented the cognitive impairment of the post-asphyxial rats at 3 months after asphyxia. Furthermore, aberrant mossy fiber sprouting in the hippocampus was more effectively prevented by the combination. We assume that either an effect on NKCC1 at the blood–brain barrier and/or cells in the periphery or the NKCC2-mediated diuretic effect of torasemide are involved in the present findings. Our data suggest that torasemide may be a useful option for improving the treatment of neonatal seizures and their adverse outcome.

DEVELOPMENT OF MUTRALA KASHAYA - A NOVEL AYURVEDIC DECOCTION

Renal calculi, one of the most common social problems caused by incorrect urine elimination. By the process of excretion of urine in excess quantity, Mutrala drugs help in the removal of renal stones through the urine or lessen their size. A novel decoction was prepared by ingredients having diuretic and lithotropic action. Mutrala kashaya was prepared by boiling coarse powder of Boerhavia diffusa Linn., Treibulus terrestris Linn., Bergenia ligulata Wall., Crateva nurvala buch Ham., Coriandrum sativum Linn., Vetivera zizanoids Linn., Benincasa hispida Thunb. and Vigna unguiculata Linn. Phyto-and physiochemical values of all drugs were under standard range of API. Total solids of Mutrala kashaya is 4.92 %, pH is 4.5, specific gravity is 1.04, refractive index is 1.349, viscosity is 0.00125 mm2 sec-1. HPTLC showed 16 Rf values. It shows presence of reducing sugars (1.5%), fats, and oils along with cardiac and saponin glycosides. Mutrala kashaya can be developed by using herbal drugs having diuretic and lithotrophic effects.

Study of Chronic Toxicity of Strawberry Garden (<i>Fragaria ananassa</i>) Leaves of Dry Extract

Introduction. Strawberry garden leaf extract dry (strawberry extract) is one of the potential substances for obtaining safe medicines for the treatment of diseases of the urinary tract, as it has diuretic and anti–inflammatory activity. The study of chronic toxicity is a mandatory step in the preclinical assessment of the safety of a new pharmacological substance.Aim. Preclinical studies of the chronic toxicity of the substance – strawberry extract.Materials and methods. The object of the study was strawberry extract obtained at JSC "Biohimmash". The study of the chronic toxicity of strawberry extract with prolonged administration to rats was carried out in the Laboratory of Medicinal Toxicology of the All-Russian Research Institute of Medicinal and Aromatic Plants in accordance with the "Guidelines for Experimental (Preclinical) Study of new pharmacological Substances" [1]. Laboratory animals were divided into three groups of 15 rats each: group I – control (water); group II – strawberry extract at a dose of 72 mg/kg; group III – strawberry extract – 720 mg/kg.Results and discussion. As a result of a 3-month experiment, it was found that strawberry extract with intragastric administration does not cause the death of animals and does not have a general toxic effect. Also, strawberry extract with intragastric application shows a stable diuretic effect and its preservation during a three-month experiment.Conclusion. Thus, the chronic toxicity of strawberry extract was studied. It was found that strawberry extract does not have a general toxic effect. The conducted research shows the prospects for further research on the development and production of medicines from strawberry leaves with dry extract, which have diuretic and anti-inflammatory activity.

Characterization of Hypolipidemic Phenol Analogues from Fermented Tea by Eurotium cristatum

Fuzhuan brick tea (FBT), a type of black tea, is a traditional beverage in China, especially popular among frontier ethnic groups. FBT is well-known for its health benefits, such as hypoglycemic, anti-hypertensive, anti-inflammatory, diuretic, and detoxification effects. Nevertheless, the underlying mechanisms on the molecular level are still elusive and the key compounds responsible for the health benefits are unidentified. Previous studies have mainly focused on functional studies of the water extract. However, FBT is typically cooked with butter or milk. Therefore, we hypothesized that some lipophilic components in FBT, which can be absorbed through the co-consumption of butter or milk, may play an important role in the health benefits. The present study aimed to investigate whether the liposoluble extract of FBT alleviates symptoms related to metabolic diseases and to identify the active compounds involved. By comparing the high-performance liquid chromatography (HPLC) profiles of water, milk and hexane extract, some low polarity peaks were observed in the milk and hexane extracts. Furthermore, the hexane extract treatment alleviated body weight gain, serum total cholesterol and triglyceride levels, and inhibited the accumulation of hepatic fat granules in a high-fat diet (HFD)-induced C57BL/6N mouse model. In order to identify the key functional lipophilic compounds in FBT, the hexane extract of FBT was subjected to chemical characterization. Four phenol analogs were characterized, namely, isodihydroauroglaucin (1), dihydroauroglaucin (2), tetrahydroauroglaucin (3), and flavoglaucin (4). Compounds 1 and 4 reduced the levels of total cholesterol and triglyceride in vivo. Both compounds also inhibited the high-fat diet-induced body weight gain and accumulation of fat granules in the liver of C57BL/6N mice. Isodihydroauroglaucin and flavoglaucin have therefore been identified as bioactive ingredients that contribute to the health benefits of FBT.

Diuretic and Natriuretic Effects of Hesperidin, a Flavanone Glycoside, in Female and Male Hypertensive Rats

Hesperidin (HSP) is a major flavanone glycoside in citrus fruits, including sweet oranges and lemons. It demonstrates numerous pharmacological activities, such as antihypertensive effects and cardiac and kidney tissue protection. However, its effect on modulating renal function has yet to be properly explored. Female and male Wistar spontaneously hypertensive rats (SHR) were used to test the effect of HSP on renal function. The rats were divided into different groups, treated orally, and placed in metabolic cages for urine collection for 8 h. HSP, at doses of 0.3-3 mg/kg, led to an increase in urine volume in both female and male SHR. This effect was associated with increased Na+ elimination (3 mg/kg) without causing any change in K+ excretion or pH and conductivity values. When given HSP in combination with hydrochlorothiazide (HCTZ) or amiloride (AMLR), urine volume and Na+ elimination were significantly increased compared to the group that received only HSP. In relation to K+ excretion, the depleting effect of HCTZ and the sparing of AMLR prevailed in both groups. Pre-treatment with a non-selective cholinergic receptor antagonist, atropine, partially prevented HSP-induced diuresis and natriuresis in male SHR, but this effect was not demonstrated with the non-selective inhibitor of the enzyme cyclooxygenase, indomethacin. This study shows the diuretic action of HSP in hypertensive rats, an activity probably associated with the cholinergic pathway. Although various biological actions have already been defined for HSP, this pioneering research reveals its potential as a diuretic medicine.

Anti-atherogenic and cardio-protective properties of sweet melon (Cucumis melo. L. Inodorus) seed extract on high fat diet induced obesity in male wistar rats

BackgroundCucumis melon is a medicinal plant with multiple pharmacological properties such as anti-inflammatory, antioxidant, and diuretic effects. An increasing body of scientific evidence established the anti-diabetic/anti-obesity effects of Cucumis melo in humans, mice, and hamster models. However, there are no tangible reports on its ability to prevent cardiovascular complications following diet-induced obesity. The anti-atherogenic and cardioprotective effects of the Methanolic extract of Cucumis melo. L. Inodorus seeds on a high-fat diet (HFD)-induced obese rats was assessed in this study. MethodsForty male Wistar rats were randomly divided into five groups, (n = 8/group); i.e., Normal (N), HFD, HFD + 50 mg/kg b.w. of MCMs (Methanolic extract of Cucumis melon seeds), HFD + 100 mg/Kg b.w. of MCMs and HFD + 200 mg/kg b.w. of MCMs. The experimental animals were anaesthetized and sacrificed after 10 weeks, and blood samples and heart tissue were collected for further analysis. Using the Graph Pad Prism version 5.0, the results expressed as Mean ± SD was tested using the one-way ANOVA to show intergroup differences, followed by Bonferonni ‘s post hoc test. The level of significance was determined at P ≤ 0.05.ResultsMCMs significantly (P < 0.05) reduced body weight, adiposity index, total fat mass, low-density lipoprotein cholesterol (LDL-c), and total cholesterol (TC) compared with the HFD obese groups MCMs caused a significant reduction in the body weight, total fat mass, adiposity index, low-density lipoprotein cholesterol (LDL-c), and total cholesterol (TC) when compared to the animals in HFD obese groups. Also, the Atherogenic index of plasma (AIP), Castelli index and, malondialdehyde (MDA) significantly (P < 0.05) decreased in MCMs treated groups compared to the HFD obese group. The catalase, protein, and HDL levels were significantly increased in MCMs treated groups compared to HFD-obese animals. Expression of nitric oxide in the form of nitrite in the heart tissue significantly increased in the MCMs treated compared to the HFD-obese rats, with the majority of the positive results recorded at 100 mg/Kg b.w. of MCMs.ConclusionsMCMs have anti-atherogenic and Cardio-protective properties on High Fat Diet-Induced Obesity in Male rats via an antioxidant and nitric oxide-dependent mechanism. Further study is recommended to evaluate the molecular mechanisms to which these anti-atherogenic and cardio-protective actions can be attributed and exploit the GCMS result in the development of drug candidates.

APPLYING STRESS AND COPING THEORY TO UNDERSTAND DIURETIC ADHERENCE EXPERIENCES IN THOSE WITH HEART FAILURE

Abstract Heart failure (HF) is a chronic and costly condition, affecting at least 6 million Americans. The ventricular dysfunction associated with HF results in fluid volume overload, which is commonly managed with diuretics. Despite the benefits of diuretics, some individuals with HF report bothersome and stressful side effects and intentionally do not adhere. Positive intrinsic motivators, such as positive emotions, may benefit individuals in their adaptation to medication-related stress. However, there has been limited study of these potential motivators in older adults with HF. The purpose of this descriptive qualitative study was to understand intrinsic factors underlying diuretic adherence in adults with HF using the transaction theory of stress and coping. Using a descriptive qualitative approach, 82 adults who were hospitalized for HF and prescribed home diuretics were interviewed. The findings of the current study revealed the ways participants appraised diuretics and how they overcame the perceived medication effects so they could adhere to the medication. Data analysis revealed three themes: (1) diuretics are bothersome (2) staying positive in the midst of hardship, and (3) adapting to endure. Adherent participants stayed positive amid the perceived medication-related hardship, maintaining resilient and grateful attitudes. Adherent participants adapted to bothersome diuretic effects and utilized creative strategies for adherence. More research is needed to understand the relationships between resilience, adaptive coping, and adherence to diuretics.

Phytochemical Screening and Diuretic Activity of the Aqueous and Ethanolic Extract of Clitoria ternatea Flowers

Clitoria ternatea, commonly known as butterfly pea, is a perennial herbaceous plant from the Fabaceae family. It has recently attracted a lot of interest as it has potential applications both in modern medicine and agriculture, and as a source of natural food colorants and antioxidants.Additionally, Clitoria ternateahas been widely used in traditional medicine, particularly as a supplement to enhance cognitive functions and alleviate symptoms of numerous ailments including fever, inflammation, pain, and diabetes.The present study was undertaken to investigate diuretic effect of aqueous and ethanolextracts of the dried flowers of Clitoria ternatea in normal rats.Qualitative analysis of various phytochemical constituents was determined by the well-known test protocol available in the literature.Aqueous and ethanol extracts of Clitoria ternateaflowers were administered to experimental ratsorally at doses of 500 mg/kg p.o. Furosemide (5 mg/kg) was used as positive control instudy. The diuretic effect of the extracts was evaluated by measuring urine volume and sodium content.Phytochemical screening of the extract showed the presence some common compounds like alkaloids, resins, steroids, tannins, saponins, and glycoside.Urine volume was significantly increased by aqueous and ethanol extracts incomparison to control group. While the excretion of sodium was also increased by both extracts.We can conclude that aqueous and ethanol extracts of Clitoria ternateaproduced notablediuretic effect which appeared to be comparable to that produced by the reference diuretic Furosemide. Thepresent study provides a quantitative basis for explaining the folkloric use of Clitoria ternateaas a diuretic agent.&#x0D; Keywords: Clitoria ternatea, Fabaceae, Phytochemical constituents, Diuretic effect, Furosemide

MEADOW MEDICINAL PLANTS IN THE VICINITY OF HOLOBORODKIVSKE VILLAGE, POLTAVA DISTRICT, POLTAVA REGION

The article presents the results of the analysis of the species composition, biomorphological and ecological features, and frequency of occurrence of meadow medicinal plants in the vicinity of Holoborodkivske village, Poltava district, Poltava region. In this area, 34 species of meadow medicinal plants belonging to 32 genera, 17 families, 3 classes and 2 divisions were identified. Representatives of two divisions were common: Equisetophyta (1 species or 2,9% of the total) and Magnoliophyta (33 species or 97,1%), and within the latter, representatives of two classes – Liliopsida (1 species or 2,9%) and Magnoliopsida (32 species or 94,2%). The most numerous by the number of species represented are the families: Asteraceae (8 species or 23,5%), Rosaceae (4 species or 11,8%), Fabaceae, Polygonaceae and Lamiaceae (3 species or 8,8% each), Caryophyllaceae (2 species or 5,9%), the remaining 16 are represented by one species (2,9%). Among the identified genera, only Artemisia L. and Persicaria Mill. have 2 species (5,9%) each, the other 30 genera have 1 species (2,9%). Herbaceous perennial plants prevail by the main biomorph (22 species or 64,7%). Hemicryptophytes (26 species or 76,5%) dominate among the life forms according to K. Raunkier. In relation to soil moisture, mesophytes (14 species or 41,2%) dominate among the meadow medicinal plants, mesophytes (14 species or 41,2%) in relation to soil moisture, mesotrophs (21 species or 61,8%) in relation to soil trophism, and heliophytes (18 species or 53%) in relation to light. The frequency of occurrence is dominated by plants that are rare (12 species or 35,3%). Given the frequency of occurrence, 18 species (53%) are not recommended for mass collection for medicinal purposes. The groups of plants with wound healing and diuretic effects dominate in terms of pharmacological action (20 species or 58.8% each).

SGLT-2 inhibitors: new effective drugs for treatment of heart failure

Introduction: SGLT-2 inhibitors having selectivity to sodium glucose cotransporter 2 were introduced on the market in 2012 as drugs for the pharmacotherapy of type 2 diabetes.Aim of the work: To summarize the current state of knowledge about the drugs: SGLT-2 inhibitors and their mechanism of action and application in cardiology.Materials and Methods: A review of the literature available in PubMed and Google Scholar database was conducted.Results: In addition to glucosuria, the diuretic effect is caused by natriuresis. A study was conducted, after which it was deduced that the natriuretic effect of empagliflozin did not depend on the degree of renal dysfunction, and was exacerbated under the influence of loop diuretics.SGLT-2 inhibitors reduce cardiac preload. Flozins also lead to a reduction in afterload.The DAPA-HF study of 4744 patients with HF, taking 10 mg of dapagliflozin or placebo. The primary outcome of the study, was data in the form of death from cardiovascular causes or exacerbation of heart failure. These accounted for 16.3% in the flozin group compared to 21.2% in the control group. Adverse events were rare. Dapagliflozin was effective in 55% of subjects, in both patients and non-diabetics with type 2 diabetes.EMPEROR-REDUCED studied the effect of taking 10 mg of emagliflozin or placebo in 3730 patients. Flozin reduced the risk of cardiovascular death and hospitalizations. Fewer deaths from any cause were also observed.Summary: Both studies highlighted significant benefits of SGLT-2 inhibitors- they reduced the risk of death from any cause and from cardiovascular causes. The therapeutic benefits, regardless of the degree of renal dysfunction, the synergy with other drugs in heart failure, and the low number of serious side effects, led to the inclusion of flozins in the latest ESC 2021 guidelines for therapy in heart failure with reduced ejection fraction, regardless of the presence of diabetes.

Xanthium spinosum L. Extracts Inhibit Breast Cancer in Mice by Apoptosis Induction and Immune System Modulation.

Plants have been considered for many years as an important source of medicine to treat different diseases. Xanthium spinosum L. (Asteraceae, Compositae) is known for its diuretic, anti-inflammatory, and sedative effects. It is also used in the treatment of several ailments, such as cancer. In order to evaluate the anticancer and immunomodulatory activities, crude ethanol extract was prepared from the aerial part of X. spinosum and then fractionated using solvents with different polarities. As well, the chemical composition of X. spinosum extract and fractions were identified using LC-MS analysis. The antitumor effect of X. spinosum was assessed in both in vitro and in vivo models. Apoptosis induction was measured in vitro using a caspase-3 activity kit. Lymphocyte proliferation and phagocytosis and pinocytosis induction were used to quantify the effect of the plant extract and fractions on acquired and innate immunity, respectively. The effect of X. spinosum extract, and fractions on the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) in murine lymphocytes was determined using a mouse-uncoated TH1/TH2 ELISA kit. Results showed that ethanol extract had the highest antiproliferative activity (IC₅₀ = 2.5 mg mL-1) against EMT6/P cell lines, while the aqueous and chloroform fractions had the highest apoptotic activity with 2.2 and 1.7 folds, respectively. On the other hand, the n-hexane fraction was the most effective in stimulating lymphocyte proliferation, whereas ethanol extract, aq. Methanol and aqueous fractions exhibited the highest phagocytic activity. As well, X. spinosum extract and fractions were able to modulate the expression of IL-2, IL-4, and IFN-γ. A remarkable decrease in tumor size was accomplished following the treatment of tumor-bearing mice with X. spinosum extract and fractions. Both aq. Methanol and chloroform fractions showed the highest percentage change in tumor size with -58 and -55%, respectively. As well, tumor-bearing mice treated with chloroform fraction demonstrated a high curable percentage with a value of 57.1%. Anyway, X. spinosum extract and fractions exhibited no toxic impact on the liver or kidney functions of the mice-treated groups. These findings may confirm that X. spinosum has favorable anticancer and immunomodulatory effects. However, additional studies are required to fully understand the mechanisms of action of this plant and the signaling pathways involved in its effects. Moreover, more testing is needed to have better insight into the apoptotic pathway and to know the exact concentration of active compounds.

Antioxidant and antimicrobial activity of Tamarix ramosissima halophyte and its application in the food industry

Tamarix ramosissima is a halophytic species with diuretic, diaphoretic, astringent, analgesic and hemostatic effects. Decoctions and infusions used for various diseases are prepared from it. Infusion of flowers is useful for stomach inflammation, decoction of branches is effective for rheumatism, infusion of leaves and bark is prescribed for diarrhea, bleeding and diseases of the spleen. Tamarix twigs are brewed like tea. In the past, a decoction of the fruits of the plant was used in the Caucasus against infertility, and a decoction of branches treated syphilis. In this work, we investigated the antioxidant and antimicrobial activity of Tamarix ramosissima inflorescence extracts as an additive in the food industry. The results showed that the inflorescences exhibit high antioxidant activity, the degree of inhibition at 20 µl of the studied material is 9 times greater. compared with ascorbic acid and 3 times compared with emoxypine. In addition, tamarisk extracts have shown noticeable antibacterial properties against the Staphylococcus aureus strain. The strongest activity was recorded in 70% of the water-alcohol extract of inflorescences at a minimum concentration of 1 to 10. These data indicate that tamarix can be considered as an interesting source of antioxidants for the therapeutic or nutraceutical industry and for food production. These indicators characterize tamarisk extracts as an object for further study, and without a doubt are promising and little-studied raw materials for the food industry

Effects of Adrenomedullin on Atrial Electrophysiology and Pulmonary Vein Arrhythmogenesis.

Adrenomedullin, a peptide with vasodilatory, natriuretic, and diuretic effects, may be a novel agent for treating heart failure. Heart failure is associated with an increased risk of atrial fibrillation (AF), but the effects of adrenomedullin on atrial arrhythmogenesis remain unclear. This study investigated whether adrenomedullin modulates the electrophysiology of the atria (AF substrate) or pulmonary vein (PV; AF trigger) arrhythmogenesis. Conventional microelectrode or whole-cell patch clamps were used to study the effects of adrenomedullin (10, 30, and 100 pg/mL) on the electrical activity, mechanical response, and ionic currents of isolated rabbit PV and sinoatrial node tissue preparations and single PV cardiomyocytes. At 30 and 100 pg/mL, adrenomedullin significantly reduced the spontaneous beating rate of the PVs from 2.0 ± 0.4 to 1.3 ± 0.5 and 1.1 ± 0.5 Hz (reductions of 32.9% ± 7.1% and 44.9 ± 8.4%), respectively, and reduced PV diastolic tension by 12.8% ± 4.1% and 14.5% ± 4.1%, respectively. By contrast, adrenomedullin did not affect sinoatrial node beating. In the presence of L-NAME (a nitric oxide synthesis inhibitor, 100 μM), adrenomedullin (30 pg/mL) did not affect the spontaneous beating rate or diastolic tension of the PVs. In the single-cell experiments, adrenomedullin (30 pg/mL) significantly reduced the L-type calcium current (ICa-L) and reverse-mode current of the sodium-calcium exchanger (NCX). Adrenomedullin reduces spontaneous PV activity and PV diastolic tension by reducing ICa-L and NCX current and thus may be useful for treating atrial tachyarrhythmia.

Abstract 13593: Rates of Acute Kidney Injury or Discontinuation After SGLT2 Inhibitor Initiation in a Real-World Cohort of Patients With Heart Failure With Reduced Ejection Fraction

Background: SGLT2 inhibitors (SGLT2i) decrease mortality and risk of hospitalizations in patients with HFrEF. SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate real-world rates of acute kidney injury (AKI) in our clinical setting that includes patients concurrently receiving high doses of loop diuretics. Methods: We abstracted patient level data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting in the University of Michigan (1/7/2016 - 2/7/2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. Secondary end points consisted of diuretic dose reduction, change in potassium, change in serum creatinine (SCr), and other side effects not requiring discontinuation. Results: The majority of patients were male (64%) with a mean LVEF of 27%. A total of 104 (52%) patients had diabetes mellitus. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3 mg. Twenty-two (11%) patients had AKI and 18 patients (9%) discontinued their SGLT2i. Yeast infection (3%), hypotension (2.5%), and AKI (2%) were the most common reasons for discontinuation. Using ROC curve analysis, the strongest predictors for AKI were A1C (AUC = 75.8, empirical confidence interval [ECI] 66.5-83.5); baseline SCr (AUC = 72.0 ECI 65.7-78.7); LVEF (AUC = 67.6 ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC = 66.0 ECI 57.5-74.6). Similarly, the strongest positive predictors for SGLT2i discontinuation were A1C (AUC = 81.1 ECI 74.8-87.2); baseline Scr (AUC = 67.4 ECI 58.7-75.5); LVEF (AUC = 68.7 ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC = 67.2 ECI 58.2-76.0). Conclusions: A1C was the strongest predictor of AKI and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. SCr, LVEF, and furosemide equivalents also predicted these outcomes.